Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription.
Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription.
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DOI：
10.1091/mbc.e10-07-0566
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发表时间：
2011-04-15
影响因子：
3.3
通讯作者：
Yoneda T
中科院分区：
文献类型：
--
作者：
Amano K;Hata K;Muramatsu S;Wakabayashi M;Takigawa Y;Ono K;Nakanishi M;Takashima R;Kogo M;Matsuda A;Nishimura R;Yoneda T
这项研究表明，Arid 5a与Sox 9相互作用，随后调节软骨形成基因Col 2a 1的组蛋白3乙酰化，并刺激软骨细胞分化。SRY-box-containing gene 9（Sox 9）是软骨细胞谱系决定和分化的重要转录因子。最近的研究表明，Sox 9控制软骨细胞特异性基因的转录与其他几个转录调控因子。为了进一步了解Sox 9在软骨细胞分化过程中影响转录事件的分子机制，我们试图鉴定Sox 9的转录伴侣并研究它们在软骨细胞分化中的作用。我们从ATDC 5 cDNA文库中分离出富含AT的相互作用结构域的蛋白5a（Arid 5a;也称为Mrf 1）作为Col 2a 1基因启动子的激活剂。Arid 5a在软骨中高度表达，并在软骨细胞分化过程中被诱导。此外，Arid 5a在细胞核中与Sox 9物理相互作用，并上调Sox 9的软骨细胞特异性作用。Arid 5a的过表达在体外和器官培养系统中刺激软骨细胞分化。相反，Arid 5a敲低抑制软骨细胞中Col 2a 1的表达。此外，Arid 5a直接与Col 2a 1基因的启动子区结合，并刺激该区域组蛋白3的乙酰化。我们的研究结果表明，Arid 5a可能直接与Sox 9相互作用，从而增强其软骨细胞特异性作用。
This study shows that Arid5a interacts with Sox9 and subsequently modulates histone 3 acetylation of a chondrogenic gene, Col2a1, and stimulates chondrocyte differentiation. SRY-box–containing gene 9 (Sox9) is an essential transcription factor in chondrocyte lineage determination and differentiation. Recent studies demonstrated that Sox9 controls the transcription of chondrocyte-specific genes in association with several other transcriptional regulators. To further understand the molecular mechanisms by which Sox9 influences transcriptional events during chondrocyte differentiation, we attempted to identify transcriptional partners of Sox9 and to examine their roles in chondrocyte differentiation. We isolated AT-rich interactive domain–containing protein 5a (Arid5a; also known as Mrf1) as an activator of the Col2a1 gene promoter from an ATDC5 cDNA library. Arid5a was highly expressed in cartilage and induced during chondrocyte differentiation. Furthermore, Arid5a physically interacted with Sox9 in nuclei and up-regulated the chondrocyte-specific action of Sox9. Overexpression of Arid5a stimulated chondrocyte differentiation in vitro and in an organ culture system. In contrast, Arid5a knockdown inhibited Col2a1 expression in chondrocytes. In addition, Arid5a binds directly to the promoter region of the Col2a1 gene and stimulates acetylation of histone 3 in the region. Our results suggest that Arid5a may directly interact with Sox9 and thereby enhance its chondrocyte-specific action.